Development of a new generation of high-throughput DNA sequencers has led to a transformation of biomedical research. These instruments provide a wide range of applications on a whole genome scale, including SNP discovery, transcriptome profiling, targeted exome sequencing and identification of protein- nucleic acid interactions. This proposal seeks funds to expand high-throughput sequencing capacity of the University of Rochester Functional Genomics Center (FGC) by addition of an Illumina HiSeqTM 2500 System next-generation DNA sequencer. Existing next-generation capabilities within the FGC are supported by a single Illumina GAIIxTM instrument. Replacement of the GAIIxTM with the new HiSeqTM 2500 would substantially expand capacity of the FGC to meet the increasing demand for high-throughput sequencing services at our two campuses, the University of Rochester School of Medicine and Dentistry (SMD) and the University of Rochester main campus (UR). As a result of a significantly larger throughput and a faster run time, access to the HiSeqTM 2500 instrument will save investigators time and cost on their research projects. This instrument will primarily be used by a group of 10 Major and 8 Minor Users who are members of an existing strong Illumina user base with a diversity of NIH funded projects. Because the HiSeqTM 2500 will replace the existing GAIIxTM in the FGC, it will be easily integrated into an established workflow without the need for additional ancillary equipment, staff or computing infrastructure. The FGC is part of an existing multi-core structure providing shared resources to SMD investigators, including DNA sequencing, microarrays, proteomics, metabolomics as well as informatics and statistical support. Support provided by the FGC for high-throughput sequencing includes initial consultation, sample preparation, library construction and sequencing. Bioinformatics and statistical support is provided through the FGC by services integrated with the Center for Integrated Research Computing (CIRC) and The Department of Biostatistics and Computational Biology. These combined resources and support will allow experienced investigators as well as investigators unfamiliar with high-throughput sequencing to take immediate advantage of the HiSeqTM 2500 capabilities. Addition of the HiSeqTM 2500 as a cost effective shared resource will provide a substantial benefit to multiple NIH funded projects and stimulate additional projects among new investigators, enabling them develop future NIH funded projects and compete at the highest scientific level.